Dealing With Infertility
"We were a couple for five years by the time we got married, so we decided to let nature take its course," she says. "It never crossed our minds that getting pregnant would be so difficult."
It seemed like everyone else was having babies, says Anthony, 39. "I have three brothers and three sisters, and they all had kids. You're happy for other people, but you want to experience it too."
An evaluation by a fertility specialist revealed no clear-cut reason for their inability to conceive naturally. What ultimately worked was a combination of a drug to induce ovulation and intrauterine insemination, a procedure in which a catheter was used to deliver Anthony's sperm directly into Heather's uterus around the time of ovulation.
The first five attempts with intrauterine insemination failed, and Heather and Anthony felt crushed each time. They finally got good news after the sixth try.
In February 2004, they found out that Heather was pregnant and due to have a baby in October. Looking back on it, Heather wishes that they had sought medical help sooner and had known more about infertility. "At the time, I felt like I was the only one with the problem," she says. But the Panseras' experience is not uncommon. According to the American Society for Reproductive Medicine (ASRM), 6 million Americans, roughly 10 percent of the population of reproductive age, face infertility.
Here are answers to frequently asked questions about infertility.
Q. What is infertility?
A.Infertility is a disease or condition of the reproductive system that interferes with the ability to conceive. It's typically defined as not being able to get pregnant after having regular unprotected sex for one year. "Regular" is considered every few days when a woman is ovulating--the time of the month when one or more eggs are released from the ovaries. Couples may want to seek medical treatment sooner than the one-year mark if the woman is over 35 or if there is a history of irregular menstrual cycles or diseases of the reproductive system.
Infertility also includes the inability to carry a pregnancy to term, as in the case of someone who's had multiple miscarriages, says Diane Clapp, director of medical information at RESOLVE, a nonprofit advocacy organization for men and women facing infertility. "Some people think that infertility is all in the head and can be fixed with relaxation or a vacation," says Clapp, who is a registered nurse. "But infertility is a medical disease that most people can be treated for." About two-thirds of people who are treated for infertility will become pregnant, according to RESOLVE.
Q. How is conception achieved?
A.Many people don't give much thought to the details of conception. But conceiving a baby is the result of a chain of events. One missed step anywhere along the way can throw everything off. First, an egg must be released during ovulation. A man's sperm must be able to reach the egg and fertilize it. The fertilized egg then must travel through the woman's fallopian tube to the uterus and be successfully implanted there. For the embryo to develop, the woman must be producing an adequate amount of hormones. For example, human chorionic gonadotropin (HCG) is a hormone that helps maintain a pregnancy. After a fertilized egg is implanted in the uterus, HCG is produced by the developing placenta, the structure that supplies nutrients to the baby.
Sometimes a couple will succeed in conceiving after identifying when the woman ovulates and having sexual intercourse around that time. Using ovulation test kits and basal thermometers can help determine more precisely when ovulation occurs. Basal thermometers can indicate a rise in body temperature, which occurs when a woman ovulates. But infertility is more than just bad timing. It can involve disorders that prevent conception or implantation from taking place.
Q. What are the primary causes of infertility?
A.For men, the primary cause of infertility is a sperm disorder. A man may have no sperm or low sperm, or there could be a problem with how the sperm is moving.
For women, the primary cause of infertility is an ovulation disorder. Normally, a woman ovulates every month, usually around the middle of the menstrual cycle, which averages 28 days. Experts say that women with an ovulation disorder may not ovulate at all or they may ovulate irregularly.
Other common causes of infertility in women are a blockage of the fallopian tubes, which prevents an egg from traveling to the uterus, and hormonal defects that make the uterine lining unprepared for egg implantation or that keep a pregnancy from being maintained.
Q. What are the main risk factors for infertility?
A.A woman's fertility starts to decrease in her early 30s and takes a big drop after age 35. According to the ASRM, a healthy 30-year-old woman has about a 20 percent chance each month of getting pregnant. By age 40, that chance is only about 5 percent.
Experts say the main reason for the drop is that women are born with all the eggs they will ever have, and the supply of eggs goes down with age. "The quality of the eggs also goes down, which increases the likelihood of miscarriage in older women," says Adelina Emmi, M.D., associate professor of reproductive endocrinology and infertility at the Medical College of Georgia. "You may hear about celebrities having twins at 50, but you don't always know the details, like whether donor eggs were used."
And though men produce sperm most of their lives and don't experience the sudden drop in fertility that women do, a man's fertility may decrease gradually over time. "As men age, their fertility declines later and less dramatically than it does in women," Emmi says. "There is also evidence that the risk of gene defects in sperm goes up with age."
The risk of infertility also goes up when either partner has had diseases or surgery that could damage the reproductive organs. For example, a major complication of sexually transmitted diseases for women is pelvic inflammatory disease (PID). This infection can lead to infertility because it causes scarring in the uterus and fallopian tubes. Men may have reproductive abnormalities due to prostate surgery or a disorder of the testes resulting in abnormal sperm production.
"This is an area of medicine where getting a good patient history really counts," Emmi says. "We can pick up all kinds of things that people may not realize affect their fertility--from chronic conditions like prediabetic states and thyroid disorder, which can interfere with ovulation, to blood pressure medication, which can lower a man's sperm count."
Lifestyle risk factors that can impair fertility in men and women include smoking, alcohol and drug use, and sexually transmitted diseases. In women, being overweight or underweight can interfere with the production of estrogen, a female hormone that regulates the menstrual cycle and ovulation. According to the ASRM, too much body fat causes a woman to produce too much estrogen. Too little body fat causes a woman to produce too little estrogen.
Q. What kinds of doctors evaluate and treat infertility?
A.Obstetrician-gynecologists (OB-GYNs) can evaluate and treat infertility in women. OB-GYNs specialize in general medical care of women, including care related to pregnancy and the reproductive tract. Urologists, who specialize in the urinary tract and the male reproductive organs, can evaluate and treat infertility in men.
More resistant and complex problems are typically handled by "fertility specialists," board-certified reproductive endocrinologists who have completed training in obstetrics and gynecology, followed by specialized training in hormonal problems and infertility. One example of a complex problem is a history of failure to conceive despite regular unprotected intercourse in a woman who has regular menstrual periods and whose male partner has normal sperm. Other examples of complex problems include a woman who has experienced multiple miscarriages or who has severely damaged fallopian tubes requiring the need for treatment with assisted reproductive technologies (ART)--the joining of eggs and sperm in a lab so that fertilization can occur.
The decision about when to ask for a referral to a fertility specialist is a personal one. Experts say that couples should consider the age of the woman, the complexity of their problems, and how they are feeling about the progress of their treatment. Consumers should be proactive about asking their doctors for a referral to a specialist and about investigating the qualifications of the specialist. A certificate of special qualification in reproductive endocrinology and infertility from the American Board of Obstetrics and Gynecology ensures that the specialist has completed a rigorous course of training.
Q. What goes into a fertility evaluation?
A.A standard fertility evaluation includes physical exams and medical and sexual histories of both partners. Men undergo a semen analysis that evaluates sperm count and sperm movement. "We look at the percent that are moving and how they are moving--are the sperm sluggish? Are they wandering?" says Robert G. Brzyski, M.D., Ph.D., associate professor of obstetrics and gynecology at the University of Texas Health Science Center at San Antonio. "Often, it's not possible to identify a specific reason for a sperm disorder," he says. "But there is new recognition that very low sperm or no sperm may be related to genetics--an abnormality of the Y chromosome."
For women, doctors first check to see whether ovulation is occurring. This can be determined and monitored through blood tests that detect hormones, ultrasound examinations of the ovaries, or an ovulation home test kit. "An irregular menstrual pattern would make us suspicious of an ovulation problem, but it's also possible for a woman with regular periods to have an ovulation disorder," Brzyski says.
If a woman is ovulating, doctors then move to a standard test called the hysterosalpingogram, a type of X-ray of the fallopian tubes and uterus. This test involves placing a radiographic dye solution into the uterine cavity. Multiple X-rays are taken. If the fallopian tubes are open, the dye will flow through the tubes and be visible in the abdominal cavity. If the fallopian tubes are blocked, the dye will be retained in the uterus or fallopian tubes, depending on the location of the blockage.
Other tests give doctors more information. For example, ultrasound can be used to examine the female reproductive structures. Hysterosonography is a more complicated type of ultrasound that involves putting salt water (saline) into the uterus during an ultrasound exam. "This is more likely to reveal structural abnormalities than regular vaginal sonography will show alone," Brzyski says. One such abnormality that hysterosonography may identify is fibroid tumors, which may distort the shape of the uterine cavity.
A surgical procedure called laparoscopy also allows doctors to examine the ovaries, uterus, fallopian tubes, and abdominal cavity. This involves inserting a fiber-optic telescope into the abdomen. One advantage of laparoscopy is that it allows doctors to both diagnose and treat conditions such as endometriosis, when uterine cells attach to tissue outside of the uterus. Adhesions, abnormal attachments between two surfaces inside the body, can also be treated in this way.
Doctors have begun to assess the ovarian reserve by measuring hormone levels and seeing how the ovaries respond to various fertility treatments. This helps evaluate the availability of eggs and the likelihood that a healthy pregnancy will result. "Some women who are 35 are fertile while others are not because their supply of eggs is depleted," Brzyski says. "In the last decade, we've learned this can be investigated through a blood test on the third day of the menstrual cycle. If the numbers are normal, it doesn't guarantee fertility. But if the numbers are abnormal, it points to a serious problem. Up to 20 percent of women who seek infertility care have an abnormal ovarian reserve test."
There are also tests that evaluate how sperm and eggs interact, as well as whether either party is developing antibodies to the sperm. This occurs when the man's or the woman's immune system recognizes the sperm as something foreign and attacks it.
Q. What does it mean when infertility is "unexplained"?
A.Sometimes a couple is told that their infertility is unexplained. This means the reason can't be identified through diagnostic tests. Even in cases of unexplained fertility, it's still possible to be treated successfully.
Researchers continue to look for clues that may shed light on unexplained infertility and improve treatment. In 2003, researchers funded by the National Institutes of Health and private sources reported the discovery that an embryo initially attaches to the uterine wall by using specialized molecules located on the surfaces of the embryo and the uterus. The embryo is able to attach because of a sticky interaction with the uterine wall.
The process is "like a tennis ball rolling over a tabletop covered with syrup," says Susan Fisher, Ph.D., the study's senior author and an anatomy professor at the University of California, San Francisco. "Understanding the molecular underpinnings of the process that initiates pregnancy is the first step in devising therapies that will improve the rate of implantation."
Q. What are the conventional treatments for infertility?
A.Conventional therapies, such as drugs or surgery, are used to treat 85 percent to 90 percent of infertility cases. Examples of reproductive surgery for men are vasectomy reversal and varicocele repair, a procedure that may restore fertility by treating varicose veins in the scrotum. Examples of fertility-related surgery for women include removal of noncancerous tumors in the uterus called fibroids, and the removal of endometriosis implants, which can cause infertility.
There are two types of ovulation drug treatments approved by the FDA. Clomid and Serophene (clomiphene citrate) are taken by mouth. Repronex and Pergonal (human gonadotropins) are injected. Both types stimulate the ovaries to produce eggs.
Clomiphene is usually the first line of treatment in women with ovulation problems. "In women who are not ovulating, 60 percent to 85 percent of women will ovulate with clomiphene, and 30 percent to 40 percent will become pregnant," says Audrey Gassman, M.D., a medical reviewer in the FDA's Division of Reproductive and Urologic Drug Products. One of the risks of ovulation-inducing drugs is that more than one fetus may result.
Drugs that stimulate ovulation are often used with intrauterine insemination, a procedure in which millions of sperm are inserted into a woman's uterus around the time of ovulation to increase the chance of pregnancy. A partner's sperm or donor sperm may be used.
Q. What are the side effects of fertility drugs?
A.Among the most common bothersome side effects of clomiphene are hot flashes, which occur in 10 percent of women. Abdominal discomfort and bloating is seen in less than 5 percent. Less common are nausea, vomiting, and breast discomfort, which occur in 2 percent of women. Gonadotropins can cause side effects similar to clomiphene. The most common serious adverse event with gonadotropins is ovarian hyperstimulation syndrome. This causes ovarian enlargement and pain and an accumulation of fluid in the abdomen that is potentially dangerous. This results in pain in the pelvic area.
The occurrence of ovarian hyperstimulation syndrome varies with the gonadotropin used, but with most gonadotropins, hyperstimulation occurs in 5 percent to 7 percent of women, with severe cases affecting less than 2 percent of patients, according to Gassman. Mild cases may result in the development of ovarian cysts. "In severe cases of this, patients may need to be hospitalized for lung, kidney, and liver problems, and deaths have been reported, but this is rare," Gassman says. People who experience bothersome side effects while taking fertility drugs should see their doctors.
The incidence of multiple pregnancies with clomiphene is about 8 percent, and the incidence of multiple pregnancies with gonadotropins is up to 20 percent. In contrast, the rate of multiple infant births is 3 percent in the general U.S. population, according to a 2001 report on ART success rates published by the Centers for Disease Control and Prevention (CDC) and the ASRM. Most of the cases of multiple pregnancies due to ovulation-stimulating drugs result in twins, according to the ASRM, but up to 5 percent result in triplets or a higher number of babies. A multiple pregnancy significantly raises the risk of preterm labor, pregnancy complications for the mother, and low birth weight and long-term disability in babies.
Q. Do fertility drugs cause ovarian cancer?
A.Concern over a link between fertility drugs and ovarian cancer came from studies published in the early 1990s that suggested the risk of ovarian cancer might be significantly increased in women exposed to ovulation drugs. "But more recent studies have failed to corroborate a strong association between fertility drugs and ovarian cancer in the general population," Gassman says.
One study, supported by the National Cancer Institute, evaluated more than 12,000 women and did not find a strong link between ovulation-stimulating drugs (clomiphene and gonadotropins) and ovarian cancer. The researchers also concluded that slight but non-significant elevations in risk with drug use among certain subgroups support the need to continue monitoring long-term risks. The study was published in the June 2004 issue of Obstetrics and Gynecology, the journal of the American College of Obstetricians and Gynecologists.
Gassman says, "The FDA continues to monitor adverse events possibly associated with these drugs and takes appropriate action when necessary based on our current understanding of the risks and benefits."
Q. What is the role of assisted reproductive technology?
A.ART is used when conventional treatment has failed or when no other treatment is available, such as when the woman's tubes cannot be repaired or the man's sperm count is very low. In vitro fertilization and embryo transfer (IVF-ET) accounts for 98 percent of ART procedures, according to the CDC.
Amy Stewart, 29, a nursing home administrator in Warrenton, Ga., turned to in vitro fertilization after exhausting other options. She was diagnosed with endometriosis in 2000 and became pregnant in 2001 after taking fertility drugs. But her pregnancy was ectopic, a dangerous condition in which the fertilized egg implants outside of the uterus, usually in the fallopian tubes. Surgery to treat the ectopic pregnancy resulted in further scarring of her fallopian tubes. She later took fertility drugs in preparation for intrauterine insemination (IUI), and had three unsuccessful IUI attempts. On the fourth IUI attempt, the procedure was canceled because the prognosis for success was poor.
To begin the IVF process, Stewart took fertility drugs to stimulate her ovaries to produce many eggs. In March 2003, her eggs were retrieved and put in a dish with her husband's sperm. About 24 hours later, they were checked to see if fertilization had taken place. It had, and the resulting embryo was transferred directly into her uterus, bypassing the fallopian tubes. Stewart found out she was pregnant on March 19, 2003, and had a baby boy in November 2003. In vitro fertilization can also be performed with donor eggs or donor sperm.
According to the CDC, in 2001, 40 percent of ART procedures that progressed to the "transfer" stage resulted in pregnancy, and 33 percent resulted in live-birth deliveries. "Transfer" refers to transfer of the embryo from an incubation vessel to the uterus. Data were collected from 385 U.S. medical centers by the Society for Assisted Reproductive Technology, an affiliate of the ASRM.
As a result of ART procedures conducted in 2001, the CDC reported that there were 29,344 live-birth deliveries and 40,687 infants total. The difference in the number of deliveries compared to infants born is due to multiple pregnancies. People who use ART are more likely to have multiple births than those who conceive naturally. This risk should be discussed with a doctor. The number of pregnancies resulting in triplets or a higher number of babies has decreased since 1999, when the ASRM updated guidelines on the number of embryos that should be transferred into the uterus.
According to the ASRM, the average cost of an IVF cycle is $12,400. Health insurance coverage for infertility depends on where consumers live and the type of services needed. As of September 2004, the following 14 states required insurers to cover some form of infertility treatment: Arkansas, California, Connecticut, Hawaii, Illinois, Maryland, Massachusetts, Montana, New Jersey, New York, Ohio, Rhode Island, Texas, and West Virginia.
Q. What other types of ART are being used?
A.IVF is the most common type of ART and there are other variations on the basic procedure, some of which remain controversial. People should learn about both the benefits and risks of any medical procedure.
- Intracytoplasmic sperm injection (ICSI):A single sperm is injected into an egg. If the egg is fertilized and develops normally, it is then transferred to the uterus. This has been a significant advance in treating men with low sperm count or disorders related to sperm movement. Couples who undergo the procedure should be aware that if their infertility is caused by a genetic defect, that defect could be passed to the child.
- Pre-implantation genetic diagnosis:An individual cell from a growing embryo is removed and used for genetic screening during IVF.
- Blastocyst culture:A blastocyst, a developed embryo, is cultured and transferred to the uterus after five or six days, compared with the three days for typical in vitro fertilization.
- Cryopreservation:Human eggs and embryos are frozen so that they can be kept viable. They are stored in liquid nitrogen at 320 degrees below zero.
- Assisted hatching:An opening is created in the egg shell surrounding the embryo to help it implant in the uterus. This procedure has not been shown to be beneficial for everyone undergoing ART. Those who may benefit from assisted hatching include couples who have preserved embryos, their own or donated, by cryopreservation, couples in which the mother is of an advanced age, or couples with a history of multiple failed IVF attempts.
The FDA does not regulate individual ART procedures, but the agency has cleared devices for use in ART procedures. Examples are biopsy devices, dissection needles, sperm and embryo delivery catheters, and solutions used to process and maintain sperm, eggs, and embryos.
Q. How can a couple deal with the emotional impact of infertility?
A.Kevin Garton, 40, of Vienna, Va., and his wife Sheryl, 38, sought counseling soon after they were diagnosed with infertility in 1994. A fertility evaluation revealed that Kevin produced no sperm. Kevin and his wife ultimately chose donor insemination, a process in which donor sperm was put into Sheryl's uterus. They now have three children.
"The whole process is a series of decisions," Garton says, "and it can be excruciating trying to figure things out." They obtained a referral to a psychiatrist who specializes in infertility. "We focused on coping and talking about why this happened to us and how we felt about it," he says. "I initially took the news very hard and felt that I had let my wife down, and I found out that she saw it as more of a joint issue." They also talked through treatment options with the psychiatrist.
Garton has been an active member of RESOLVE and feels that the support system has been critical in helping him and his wife deal with infertility. "People don't mean to say insensitive things, but when a couple says something like they accidentally got pregnant, it just crushes a person with infertility," Garton says. "It's important to have a group of people to talk with who are going through the same thing you are."
After they chose donor insemination, they had to deal with a range of issues, from how to choose a donor to how to discuss it with family, friends, and the children. "What it came down to for us," Garton says, "is that whether you conceive naturally, get medical treatment, or adopt, your kids are your kids. When you are diagnosed with infertility, you think you're different in some way at first. But I'm just a regular person who wanted to make a family."